Ibuclin^® (Tablets) Instructions for Use

Marketing Authorization Holder

Dr. Reddy’s Laboratories Ltd. (India)

Contact Information

Dr. Reddy’s Laboratories Ltd. (India)

ATC Code

M01AE51 (Ibuprofen in combination with other drugs)

Active Substances

Ibuprofen (Rec.INN registered by WHO)

Paracetamol (Rec.INN registered by WHO)

Dosage Form

Ibuclin®

Film-coated tablets, 400 mg+325 mg: 10, 20, or 200 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets orange in color, capsule-shaped, with a score on one side; the cross-section shows a white or almost white core.

Excipients: microcrystalline cellulose – 120 mg, corn starch – 76 mg, glycerol – 3 mg, sodium carboxymethyl starch (type A) – 7 mg, colloidal silicon dioxide – 5 mg, talc – 8 mg, magnesium stearate – 6 mg.

Coating composition: hypromellose 6 cps – 11.32 mg, sunset yellow FCF aluminum lake (E110) – 1.78 mg, macrogol 6000 – 2.2 mg, talc – 4.06 mg, titanium dioxide – 0.16 mg, polysorbate 80 – 0.16 mg, sorbic acid – 0.16 mg, dimethicone – 0.16 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (20) – cardboard packs.

Clinical-Pharmacological Group

Combination analgesic-antipyretic

Pharmacotherapeutic Group

Combined analgesic agent (NSAID + non-narcotic analgesic agent)

Pharmacological Action

A combined drug, the action of which is determined by its constituent components.

Ibuprofen is an NSAID that has analgesic, anti-inflammatory, and antipyretic effects. By inhibiting COX-1 and COX-2, it disrupts arachidonic acid metabolism, reduces the amount of prostaglandins (mediators of pain, inflammation, and hyperthermic response) both at the site of inflammation and in healthy tissues, and suppresses the exudative and proliferative phases of inflammation.

Paracetamol non-selectively blocks COX, mainly in the CNS, and has little effect on water-salt balance and the gastrointestinal mucosa. It has analgesic and antipyretic effects. In inflamed tissues, peroxidases neutralize the effect of paracetamol on COX-1 and COX-2, which explains its low anti-inflammatory effect.

The effectiveness of the combination is higher than that of the individual components. It relieves arthralgia at rest and during movement, reduces morning stiffness and joint swelling, and helps increase the range of motion.

Pharmacokinetics

Ibuprofen

Absorption and Distribution

Absorption is high; it is rapidly and almost completely absorbed from the gastrointestinal tract. T_max after oral administration is about 1-2 hours. Plasma protein binding is more than 90%. It slowly penetrates into the joint cavity, accumulates in the synovial fluid, creating higher concentrations there than in the blood plasma.

Metabolism and Excretion

After absorption, about 60% of the pharmacologically inactive R-form is slowly transformed into the active S-form. It undergoes metabolism.

T_1/2 is about 2 hours. More than 90% is excreted by the kidneys (unchanged no more than 1%) and, to a lesser extent, with bile as metabolites and their conjugates.

Paracetamol

Absorption and Distribution

Absorption is high; plasma protein binding is less than 10% and increases slightly in overdose. Sulfate and glucuronide metabolites do not bind to plasma proteins even at relatively high concentrations. C_max is 5-20 µg/ml, T_max is 0.5-2 hours. It is distributed fairly evenly in body fluids. Penetrates the blood-brain barrier. Less than 1% of the administered dose of paracetamol passes into breast milk.

Metabolism

About 90-95% of paracetamol is metabolized in the liver to form inactive conjugates with glucuronic acid (60%), taurine (35%), and cysteine (3%), as well as a small amount of hydroxylated and deacetylated metabolites. A small portion of the drug is hydroxylated by microsomal enzymes to form the highly active N-acetyl-p-benzoquinone imine, which binds to the sulfhydryl groups of glutathione. When liver glutathione stores are depleted (in case of overdose), hepatocyte enzyme systems can be blocked, leading to the development of necrosis.

Excretion

T_1/2 is 2-3 hours. It is excreted by the kidneys, mainly as glucuronide and sulfate conjugates (less than 5% unchanged).

Pharmacokinetics in Special Clinical Cases

In patients with liver cirrhosis, T_1/2 increases somewhat.

In elderly patients, the clearance of the drug decreases and T_1/2 increases.

In children, the ability to form conjugates with glucuronic acid is lower than in adults.

Indications

• Symptomatic treatment of infectious and inflammatory diseases (common cold, influenza) accompanied by fever, chills, headache, muscle and joint pain, sore throat;
• Myalgia;
• Neuralgia;
• Back pain;
• Joint pain, pain syndrome in inflammatory and degenerative diseases of the musculoskeletal system;
• Pain from bruises, sprains, dislocations, fractures;
• Post-traumatic and postoperative pain syndrome;
• Toothache;
• Primary dysmenorrhea.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use; it does not affect the progression of the disease.

ICD codes

Dosage Regimen

The drug is taken orally (before or 2-3 hours after meals), without chewing, with a sufficient amount of water.

Adults – 1 tablet 3 times/day. The maximum daily dose is 3 tablets.

Children over 12 years old (body weight over 40 kg) – 1 tablet 2 times/day.

The duration of treatment should not exceed 3 days as an antipyretic and not more than 5 days as an analgesic. Continuation of treatment with the drug is possible only after consultation with a doctor.

Adverse Reactions

From the digestive system NSAID-gastropathy – nausea, vomiting, heartburn, anorexia, discomfort or pain in the epigastrium, diarrhea, flatulence; rarely – erosive and ulcerative lesions, bleeding; impaired liver function, hepatitis, pancreatitis; irritation or dryness in the oral cavity, mouth pain, ulceration of the gum mucosa, aphthous stomatitis; constipation.

From the nervous system and sensory organs headache, dizziness, insomnia, anxiety, nervousness, irritability, agitation, drowsiness, depression, confusion, hallucinations; rarely – aseptic meningitis (more often in patients with autoimmune diseases); hearing loss, tinnitus, visual disturbances, toxic optic nerve damage, blurred vision or diplopia, scotoma, amblyopia.

From the cardiovascular system heart failure, increased blood pressure, tachycardia.

From the hematopoietic system anemia (including hemolytic and aplastic), thrombocytopenia, thrombocytopenic purpura, agranulocytosis, leukopenia.

From the respiratory system shortness of breath, bronchospasm.

From the urinary system: allergic nephritis, acute renal failure, nephrotic syndrome, edema, polyuria, cystitis.

Allergic reactions skin rash, itching, urticaria, angioedema, bronchospasm, dyspnea, allergic rhinitis, dryness and irritation of the eyes, swelling of the conjunctiva and eyelids, eosinophilia, fever, anaphylactic shock, erythema multiforme exudativum (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Laboratory parameters decreased serum glucose concentration, decreased hematocrit and hemoglobin, increased bleeding time, increased serum creatinine concentration, increased activity of hepatic transaminases.

Other increased sweating.

With long-term use in high doses: ulceration of the gastrointestinal mucosa, bleeding (gastrointestinal, gingival, uterine, hemorrhoidal), visual impairment (impaired color vision, scotoma, amblyopia).

Contraindications

• Peptic ulcer of the stomach and duodenum in the acute phase;
• Gastrointestinal bleeding;
• Severe renal failure (creatinine clearance less than 30 ml/min);
• Complete or incomplete combination of bronchial asthma, recurrent nasal and sinus polyposis and intolerance to acetylsalicylic acid or other NSAIDs (including in history);
• Optic nerve damage;
• Genetic absence of glucose-6-phosphate dehydrogenase;
• Blood system diseases;
• Period after coronary artery bypass grafting;
• Progressive kidney disease,
• Severe hepatic failure or active liver disease;
• Confirmed hyperkalemia;
• Active gastrointestinal bleeding;
• Inflammatory bowel diseases;
• Children under 12 years of age;
• III trimester of pregnancy;
• Increased individual sensitivity to the components of the drug (including to other NSAIDs).

With caution coronary artery disease, chronic heart failure, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial diseases, smoking, creatinine clearance less than 60 ml/min, history of gastrointestinal ulcerative lesions, presence of Helicobacter pylori infection, elderly age, long-term use of NSAIDs, alcoholism, severe somatic diseases, simultaneous use of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), viral hepatitis, mild or moderate hepatic and/or renal failure, benign hyperbilirubinemias (Gilbert’s syndrome, Dubin-Johnson syndrome, Rotor syndrome), liver cirrhosis with portal hypertension, nephrotic syndrome.

Use in Pregnancy and Lactation

In the I and II trimesters of pregnancy, use is possible only as prescribed by a doctor in cases where the potential benefit outweighs the possible risk to the mother and the potential risk to the fetus. The use of the drug in the III trimester of pregnancy is contraindicated.

If it is necessary to use the drug during lactation (breastfeeding), breastfeeding should be discontinued.

In experimental studies, no embryotoxic, teratogenic, or mutagenic effects of the components of the drug Ibuclin^® were established.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure or active liver disease.

The drug should be used with caution in viral hepatitis, mild or moderate hepatic failure, benign hyperbilirubinemias (Gilbert’s syndrome, Dubin-Johnson syndrome, Rotor syndrome), liver cirrhosis with portal hypertension.

Use in Renal Impairment

Contraindicated in severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney disease.

The drug should be used with caution in mild or moderate renal failure, nephrotic syndrome.

Pediatric Use

Contraindicated in children under 12 years of age.

Geriatric Use

The drug should be taken with caution in the elderly.

Special Precautions

Concomitant use of the drug with other medicines containing Paracetamol and/or NSAIDs should be avoided. If the drug is used for more than 5-7 days as prescribed by a doctor, peripheral blood counts and liver functional state should be monitored.

When used concomitantly with indirect anticoagulants, indicators of the blood coagulation system should be monitored.

Concomitant administration of the drug Ibuclin^® with other NSAIDs should be avoided.

To avoid possible damaging effects on the liver, alcohol should not be consumed during the drug intake.

The drug may distort the results of laboratory tests in the quantitative determination of serum glucose, uric acid, 17-ketosteroids (the drug should be discontinued 48 hours before the test).

Effect on ability to drive vehicles and machinery

During the treatment period, the patient should refrain from engaging in potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Overdose

Symptoms: gastrointestinal disorders (diarrhea, nausea, vomiting, anorexia, epigastric pain), increased prothrombin time, bleeding after 12-48 hours, lethargy, drowsiness, depression, headache, tinnitus, impaired consciousness, cardiac arrhythmias, decreased blood pressure, manifestations of hepatotoxicity and nephrotoxicity, convulsions, possible development of hepatonecrosis.

Treatment if an overdose is suspected, the patient should immediately seek medical help. Gastric lavage is recommended within the first 4 hours; alkaline drinking, forced diuresis; activated charcoal orally, administration of SH-group donors and glutathione synthesis precursors – methionine 8-9 hours after overdose and N-acetylcysteine orally or intravenously – after 12 hours, antacid drugs; hemodialysis; symptomatic therapy. The need for additional therapeutic measures (further administration of methionine, intravenous administration of N-acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as the time elapsed after its intake.

Drug Interactions

When the drug Ibuclin^® is used concomitantly with other medicines, various interaction effects may develop.

When taken concomitantly with acetylsalicylic acid, Ibuprofen reduces its anti-inflammatory and antiplatelet effect (an increase in the frequency of acute coronary insufficiency is possible in patients receiving low doses of acetylsalicylic acid as an antiplatelet agent after starting Ibuprofen).

Combination with ethanol, glucocorticosteroids, corticotropin increases the risk of erosive and ulcerative lesions of the gastrointestinal tract.

Ibuprofen enhances the effect of direct (heparin) and indirect (coumarin and indandione derivatives) anticoagulants, thrombolytic agents (alteplase, anistreplase, streptokinase, urokinase), antiplatelet agents, colchicine – the risk of hemorrhagic complications increases.

It enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs.

It weakens the effects of antihypertensive drugs and diuretics (by inhibiting the synthesis of renal prostaglandins).

It increases the blood concentration of digoxin, lithium preparations, and methotrexate.

Caffeine enhances the analgesic effect of ibuprofen.

Cyclosporine and gold preparations increase nephrotoxicity.

Cefamandole, cefoperazone, cefotetan, valproic acid, plicamycin increase the incidence of hypoprothrombinemia.

Antacids and cholestyramine reduce the absorption of the drug.

Myelotoxic drugs contribute to the manifestation of the hematotoxicity of the drug.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 5 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.